Polypeptide uploaded efficient nanophotosensitizers to overcome photodynamic resistance for enhanced anticancer therapy
2021
Abstract Being either minimally invasive or non-invasive, photodynamic therapy (PDT) has garnered much attention in treatment of superficial tumors. However, repeated irradiation of tumors may lead to PDT resistance, mediated by cell survival pathways, and may result in decreased PDT efficiency and increased emotional burden of patients. Herein, we describe a high-performance nanosystem based on N,S-codoped graphene quantum dots (GQDs), established to overcome PDT resistance in cancer via uploading cyclic (RGDfC) peptide. The as-prepared cRGD-GQDs possessed good biocompatibility, high singlet oxygen quantum yield (ΦΔ = 0.95), and excellent pH stability. Owing to the specific binding ability between c(RGDfC) and integrin αvβ3, the cRGD-GQDs could successfully aggregate in tumor cells and continuously generate high levels of reactive oxygen species (ROS). Notably, some PDT resistance-related factors, such as antioxidant proteins (Nrf2, HO-1, and NQO-1) and the pump protein ABCG2, were maintained at a low level after repetitive PDT treatment mediated by cRGD-GQDs. However, significant upregulation of these factors can be determined after repetitive PDT treatment with free GQDs. Thus, the cRGD-GQDs exhibited powerful antitumor PDT effects both in vitro and in vivo by inhibiting the survival pathways of cancer cells. In conclusion, this study presents a potential appealing clinical strategy in overcoming the acquired PDT resistance and has far-reaching significance for the future PDT therapies.
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